The Trump administration’s latest effort to reduce drug costs is expanding to biosimilars, drugs that are very similar to biologic drugs made from or isolated from living organisms such as cells. Just as a generic drug is a less expensive version of a brand-name product, biosimilars are cheaper versions of complex biological drugs. But there are key differences in the way these drugs are tested and reviewed.
Generic drugs, such as small molecules formulated in pill form, only need to show bioequivalence to the reference product, the original drug. No clinical trials are required to support a submission to the FDA. Since the first biosimilar gained FDA approval in 2015, these medications have had to undergo clinical testing to show comparable efficacy to the original product. Comparative effectiveness studies (CES) are long and expensive. According to the FDA, these tests can take up to three years at an average cost of $24 million. The time a biosimilar spends in these studies is the time patients need to continue taking a more expensive brand-name biologic.
The FDA on Wednesday announced draft guidance to reduce what it characterizes as “unnecessary clinical testing” of biosimilars. Instead of these studies, the regulator proposes allowing biosimilar manufacturers to use analytical tests. In the draft guidance, the FDA said the agency has gained significant experience in evaluating analytical differences between proposed biosimilars and their reference products, as well as understanding the impact those differences have on a product’s clinical performance.
“In addition, currently available analytical technologies can structurally characterize highly purified therapeutic proteins and model functional effects in vivo with a high degree of specificity and sensitivity using in vitro biological and biochemical assays,” the guide states. “A Comparative Analytical Assessment (CAA) is generally more sensitive than a CES in detecting differences between two products, if any, that may preclude a demonstration of biosimilarity.”
Some biosimilars undergo a “switch study,” an additional clinical trial intended to demonstrate that switching from the reference product to the biosimilar does not increase safety risks or decrease efficacy. These studies are performed for medications that must demonstrate interchangeability with a brand-name product. Biosimilar insulins are examples of products that undergo interchangeable studies. Testing for interchangeability is not required for generic drugs. In Wednesday’s announcement, the FDA said these additional tests can slow development and create public confusion about the safety of a biosimilar. The regulator now says it generally does not recommend switching studies.
A faster regulatory pathway for biosimilars could have a big financial impact for patients. Biologic drugs include AbbVie’s expensive immune drug Humira, which at its peak was the most prescribed and most expensive drug on the market. Lower-cost Humira biosimilars were launched in 2023. The FDA estimates that biologics account for just 5% of prescriptions in the U.S., but they account for 51% of total drug spending as of 2024.
To date, the FDA has approved 76 biosimilars. Only about 10% of biologic drugs expected to lose patent protection in the next decade currently have a biosimilar in development, the FDA said. In the FDA announcement, Commissioner Marty Makary said biosimilars hold the promise of significantly reducing healthcare costs.
“By streamlining the biosimilar development process and helping advance interchangeability, we can achieve massive cost reductions for advanced treatments for cancer, autoimmune diseases and rare disorders that affect millions of Americans,” Makary said.
The draft guidance, “Scientific Considerations for Demonstrating Biosimilarity to a Reference Product: Updated Recommendations for Evaluating the Need for Comparative Effectiveness Studies,” is open for comment over the next 60 days. Electronic comments can be submitted here.
The FDA’s biosimilar announcement follows an initiative the agency has introduced for generic drugs. In early October, Makary announced a pilot program that allows for faster regulatory review for generics whose bioequivalence testing is performed in the U.S. Eligible drugs must also be manufactured in the U.S. using domestically sourced active pharmaceutical ingredients.
Photo: Getty Images, Sarah Silbiger